Investigational New Drug Applications (INDA)
Investigational
New
Drug
Application
[INDA]
1
2
In
t
r
o
d
ucti
o
n
What
is
an
IND
?
An
IND
is
a
submission
to
the food
and
drug
administration
(FDA)
requesting
permission
to
initiate
a clinical
study
of
a
new
drug
product.
The
Federal
Food
,
Drug
a
n
d
Cos
m
etic
ac
t
r
equ
ir
es
that
drugs
have
a
n
approved
marketing
application
before
they
can
be
shipped
in
interstate
commerce.
The
IND
application
allows
a
company
to
initiate
and
conduct
clinical
studies
for
their
new drug
products.
The
IND
application
provides
the
FDA
with
the
data
necessary
to
decide
whether
the
new
drug
and
the
proposed
clinical
trial
pose
a
reasonable
risk
to
the
human
subjects
participating
in
the
study.
3
FDA's
role
in
the
development
of
a
new
drug
begins
when
the
drug's
sponsor
has
screened
the
new
molecule
for
pharmacological
activity
and
acute
toxicity
potential
in
animals,
wants
to
test
its
diagnostic
or
therapeutic
potential
in
humans
The
molecule
changes
in
legal
status
under
the
Federal
Food,
Drug,
and
Cosmetic
Act
and
becomes
a
new
drug
subject
to
specific requirements
of
the
drug
regulatory
system
Drug
is
to
be
the subjected
to
an
approved
marketing application
before it
is transported
or
distributed
across state
lines
IND-
notice
of
claimed
investigational
exemption
for
a
new
drug
must
be
filed
with
regulatory
body.
What
is
an
IND
?
4
Importance
of
INDA
An IND
is
required
any
time
I
want
to
conduct
a
clinical
trial
of
an
unapproved
drug.
An IND
would
be
required
to
conduct
a
clinical
trail
if
the
drug
is
a
new
chemical
entity
,
not
approved
for
the
indication
under
investigation
in
a
new
dosage
form.
Being
administered
at
a
new
dosage
level.
in
combination
with
another
drug
and
the
combination
is
not
approved.
All
clinical
studies
where
a
new
drug
is
administered
to
human
subjects
,
regardless
of
whether
the
drug
will
be
commercially
developed
,
require
an
IND.
5
When
you
don’t
need
an
IND
An
IND
is
not
required
to
conduct
a
study
if
the
drug
:
It
is
not
intended
for
human
subjects
,
but
is
intended
for
in
vivo
testing
or
lab
research
animals
(non
clinical
studies).
It
is an
approved
drug
and
the
study
is
within
its
approved
indication
for
use.
6
TYPES
OF
IND
Investigator
IND
o
Submitted
by
a
physician
who
both
initiates
and
conducts
an
investigation,
and
under
whose
immediate
direction
the
investigational
drug
is
administered or
dispensed.
o
Physician
might
submit
a
research
IND
to
propose
studying
an
unapproved
drug,
or
an
approved
product for
a
new
indication
or in
a
new
patient
population
Emergency
Use
IND
o
Allows
FDA
to
authorize
use
of
an
experimental
drug
in
an
emergency
situation
o
Does
not
allow
time
for
submission
of
an
IND
in
accordance
with
21CFR
,
Sec.
312.23
or
Sec.
312.34
Treatment
IND
o
Submitted
for
experimental
drugs
showing
promise
in
clinical
testing
for
serious
or
immediately life-threatening conditions while
the final
clinical
work
is conducted
and the
FDA
review
takes
place
7
CLASSIFICATION
OF
IND
Commercial
o
Permits
sponsor
to
collect
data
on
clinical
safety
and
effectiveness
needed
for
application
for
marketing
in
the
form
of NDA
Research
(non-commercial)
o
Permits
the
sponsor
to
use
drug
in
research
to
obtain
advanced
scientific
knowledge
of
new
drug
o
No
plan
to
market
the
product
CONTENT
OF
IND
In
three
broad
areas:
Animal
Pharmacology
and
Toxicology
Studies
–
o
An
assessment
as
to
whether
the
product
is
reasonably
safe
for
initial
testing
in
humans
o
Any
previous
experience with
the
drug
in
humans
Manufacturing
Information
o
composition,
manufacturer,
stability,
and
controls
used
for
manufacturing
the
drug
Clinical Protocols
and
Investigator
Information
o
C
o
mm
i
t
m
e
n
ts
to
obt
a
in
i
n
f
o
r
m
ed
c
o
nsent
f
r
o
m
t
h
e
research
su
b
j
ec
ts,
to
obtain
review
of
the
study
by
an
institutional
review
board
(IRB),
and
to
adhere
to
the
investigational
new drug
regulations.
O
n
ce
the
I
ND
is
sub
m
i
t
t
ed,
t
h
e
sponsor
m
u
st
wa
i
t
30
days
be
f
ore
8
i
n
it
i
ating
a
ny
c
lin
i
c
a
l
tr
ia
l
s.
D
ur
i
ng
t
h
is
ti
m
e,
FDA
has
an
oppor
t
u
n
ity
t
o
review
the
IND
for
saf
e
ty
t
o
assu
re
t
h
at
re
s
e
ar
c
h
subjects
will
not
be subjected
to
unreasonable
risk
FORMAT
OF
INDA
A.
Cover
sheet
(Form
FDA-1571)
o
Name,
address,
telephone
of
sponsor
o
Identification
of
phases
o
Commitment
not
to begin
CT
until
IND
approval
o
Commitment
by
IRB-
Form
56
o
Commitment
for conducting
CT-
accordance
with
regulations
o
Name,
title
–
Monitor
o
Name,
title
–
person(s)
for
reviewing
o
Name,
Address
of
CRO,
if
any
o
Signature
of
sponsor
B.
Table
of
contents
C.
Introductory
statement
&
general
investigational
plan
D.
Investigators
brochure
E.
Study
protocol
F.
Investigator
facilities
&
IRB
data
G.
Chemistry
manufacturing
&
control
data
H.
Pharmacology
&
toxicology
data
I.
P
1
9
r
-
e
0
6
v
-
2
i
0
o
1
u
6
s
h
u
m
an
e
x
p
erience
10
Resources
For
IND
Applications
•
Pre-Investigational
New
Drug
Application
(IND)
Consultation
Program
o
Offered
by
CDER
(Center
for
Drug
Evaluation
and
Research)
to
foster
early
communications
between
sponsors
and
new
drug
review
divisions
in
order
to
provide
guidance
on
the
data
necessary
to
warrant
IND
submission.
•
Guidance
Documents
for
INDs
o
documents are prepared
for
FDA review
staff
and applicants/sponsors to provide
guidelines to the processing, content, and evaluation/approval of applications and
also
to
the design,
production,
manufacturing,
and
testing
of
regulated
products
19-06-2016
Sagar
Kishor
Savale
11
GUIDANCE
DOCUMENTS
For
The
Complete
List
Of
CDER
Guidance,
Please
See
The
Guidance
Index
Safety
Reporting
Requirements
for
INDs
and
BE/BA
Studies
CGMP
for
Phase
1
Investigational
Drugs
Exploratory
IND
Studies
Content
and
Format
of
Investigational
New
Drug
Applications
(INDs)
for
Phase
1
Studies
of
Drugs,
Including
Well
Characterized,
Therapeutic,
Biotechnology-Derived
Products
Q
&
A
-
Content
and
Format
of
INDs
for
Phase
1
Studies
of
Drugs,
Including
Well-
Characterized,
Therapeutic,
Biotechnology-Derived
Products
Bioavailability
and
Bioequivalence
Studies
for
Orally
Administered
Drug
Products
IND
Exemptions
for
Studies
of
Lawfully
Marketed
Drug
or
Biological
Products
for
the
Treatment
of
Cancer
Guideline
for
Drug
Master
Files
A
Drug
Master
File
(DMF)
is
a
submission
to
the
Food
and
Drug
Administration
(FDA)
that
may
be
used
to
provide
confidential
detailed
information
about
facilities,
processes,
or
articles
used
in
the
manufacturing,
processing,
packaging,
and
storing
of
one
or
more
human
drugs
.
Required
Specifications
for
FDA's
IND,
NDA,
and
ANDA
Drug Master
File
Binders
Immunotoxicology
Evaluation
of
Investigational
New
Drugs
12
Laws,
regulations,
Policies,
Procedures
•
The
Federal Food, Drug, and Cosmetic
Act
is the
basic
food and
drug
law of the
U.S
The
law
is
intended to assure consumers
that
foods are pure
and wholesome,
safe
to
eat, and produced under sanitary conditions; that drugs
and
devices
are
safe and
effective
for their intended uses; that
cosmetics
are safe and made
from
appropriate
ingredients;
and
that
all
labeling
and
packaging
is
truthful,
informative,
and
not
deceptive.
13
•
Code Of Federal
Regulations
(CFR)
o
The
final
regulations
published
in
the
Federal
Register
(daily
published
record
of
proposed
rules,
final
rules,
meeting
notices,
etc.)
are
collected
in
the
CFR.
o
The
CFR
is
divided
into
50
titles
that
represent
broad
areas
subject
to
Federal
regulations.
o
The
FDA's
portion
of
the
CFR
interprets
the
The
Federal
Food,
Drug,
and
Cosmetic
Act
and
related
statutes.
Section
21
of
the
CFR
contains
most
regulations
pertaining
to
food
and
drugs.
Laws,
regulations,
Policies,
Procedures
14
•
CDER's
Manual
of
Policies
and
Procedures
(MaPPs)
MaPPS
are
approved
instructions
for
internal
practices
and
procedures
followed
by
CDER
staff
to
help
standardize
the
new
drug
review
process
and
other
activities.
Laws,
regulations,
Policies,
Procedures
INDA
Review
P
r
ocess
19-06-2016
Sagar
Kishor
Savale
15
DRUG
DEVELOPMENT
PROCESS
19-06-2016
Sagar
Kishor
Savale
16
N
e
w
D
r
u
g
D
e
v
e
l
o
p
m
e
n
t
a
n
d
R
e
v
i
e
w
P
r
o
c
e
s
s
Steps
from
Test
Tube
to New
Drug
Application
Review
17
19-06-2016
Sagar
Kishor
Savale
18
Phases
of
clinical
testing
Clinical
Trials
10-15
years from
lab
to
US
patients
Only
1
in
5000 compounds
make
it
to human
testing
Only
1 in
5
tested
in
humans
is approved
Testing
Phases
in
Humans
DISCOVERY
Phase I
RESEARCH
Phase
II
DEVELOPMENT
Phase
III
CLINICAL
STUDIES
Phase
IV
MEDICINE
APPROVED
19
20
Introductory
statement
Description
of
the
investigational
drug
All
active
ingredients
Drug’s
pharmacological
classification
Structural
formula
Route
of
administration
Summary
of
previous
human
experience
Formulation
of
dosage
forms
Objective
and
planned
duration
of
proposed
clinical
investigation.
21
Investigational
plan
Description
of clinical
studies
planned
for
the
experimental
drug
Purpose
of
the
study
Indication
to
be
studied
Types
of
trials
to
be
initiated
1.
Number
of
study
subjects
2.
Risks
involved
22
INVESTIGATORS
BROCHURE
Structural
formula
of
drug.
Summary
of
pharmacological
,
toxicological
,
pharmacokinetic
effects
in
animals.
Safety
and
efficacy
Purpose
of
study
Dose
/
dose
frequency
Monitoring
procedures
23
Clinical
protocol
A
clinical
protocol
describes
how
a
particular
clinical
trial
is
to
be
conducted.
It
describes
the
objectives
of
study
the
trial
design
how
subjects
are
selected
how
the
trial
is
to
be
carried
out
24
It should
contain
the following
elements:
A
statement
of the
objective
and
purpose
of
study.
Name
, address and
qualification
of each
investigator
participating
in
the
study.
Name
and
address
of
each
clinical
site.
Study
subject
inclusion
and
exclusion
criteria.
Estimate
of the
number
of subjects
to
be enrolled
in
the
study.
25
Chemistry,
manufacturing
and
Control
Data
Determines
the adequacy
of
methods
used
to
manufacture
and
assay
investigational
compound
Safety
concerns
Describe
drug
substances
Method
of
preparation
Reagent
and
solvents
Acceptable
limits
and
analytical
methods
to
ensure
quality
and
purity
of
drug.
26
Pharmacological
and
Toxicology
data
:
Pharmacology
and
drug
disposition
Integrated
toxicology
summary
Previous
human
exposure
:
Marketed
(foreign)
or
previously
tested
in
humans.
FDA
Review
of
The
INDA
Once
the
ind
is
stamped
as
received
,it
is
sent
to
the
review
division
within
CDER.
On
arrival
at
the
review
division
, it
is
critically
evaluated
by
several
reviewers
of
Chemisty
Biopharmaceutics
Medical
Stastistics
Microbiology
Pharmacology
/toxicology
sections
28
All
these
areas
review
the
data
submitted
with
the
primary
purpose
to
ensure
safety
of
the
individual
enrolled
in
th
e
study.
Once
an
IND
is
submitted,the
study
can’t
be
initiated
until
a
period
of
30
days.
If
there
are
any
major
issues
relating
to
the
safety
of
the
volunteers
in
the
proposed
study
,
the
FDA
can
institute
a clinical
hold.
29
INDA
Annual
r
eports
Sponsors
should
submit
an
annual
report
that
provides
the
FDA
with
a
brief
update
on the
progress of
all
investigations
included
in
the
IND.
It should
contain
the following:
Individual
study
information.
Summary
of
the
study.
Listing
of any significant
foreign
marketing
developments
with
the
drug
e.g.
approval
in
another
country.
30
An Investigational New Drug Application (INDA) is a crucial submission to the FDA for permission to conduct clinical studies on new drug products. It plays a pivotal role in assessing the safety and efficacy of new drugs before they can be marketed and distributed for human use. This article covers the definition of an IND, the FDA's role in drug development, the importance of an INDA, scenarios where an IND is not needed, and different types of IND submissions. Understanding the process and significance of an INDA is essential for pharmaceutical companies aiming to bring new drugs to market.
Download Presentation
Please find below an Image/Link to download the presentation.
The content on the website is provided AS IS for your information and personal use only. It may not be sold, licensed, or shared on other websites without obtaining consent from the author. Download presentation by click this link. If you encounter any issues during the download, it is possible that the publisher has removed the file from their server.
E N D
Presentation Transcript
Investigational New Drug Application [INDA] 1
Introduction What is an IND ? An IND is a submission to the food and drug administration (FDA) requesting permission to initiate a clinical study of a new drug product. The Federal Food , Drug and Cosmetic act requires that marketing application before they can be shipped in interstate commerce. drugs have an approved The IND application allows a company to initiate and conduct clinical studies for their new drug products. The IND application provides the FDAwith the data necessary to decide whether the new drug and the proposed clinical trial pose a reasonable risk to the human subjects participating in the study. 2
What is an IND ? FDA's role in the development of a new drug begins when the drug's sponsor has screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans The molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system Drug is to be the subjected to an approved marketing application before it is transported or distributed across state lines IND- notice of claimed investigational exemption for a new drug must be filed with regulatory body. 3
Importance of INDA An IND is required any time I want to conduct a clinical trial of an unapproved drug. An IND would be required to conduct a clinical trail if the drug is a new chemical entity , not approved for the indication under investigation in a new dosage form. Being administered at a new dosage level. in combination with another drug and the combination is not approved. All clinical studies where a new drug is administered to human subjects , regardless of whether the drug will be commercially developed , require an IND. 4
When you dont need an IND An IND is not required to conduct a study if the drug : It is not intended for human subjects , but is intended for in vivo testing or lab research animals (non clinical studies). It is an approved drug and the study is within its approved indication for use. 5
TYPES OFIND InvestigatorIND o Submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. o Physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population Emergency Use IND o Allows FDAto authorize use of an experimental drug in an emergency situation o Does not allow time for submission of an IND in accordance with 21CFR , Sec. 312.23 or Sec. 312.34 Treatment IND o Submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDAreview takes place 6
CLASSIFICATION OF IND Commercial o Permits sponsor to collect data on clinical safety and effectiveness needed for application for marketing in the form of NDA Research (non-commercial) o Permits the sponsor to use drug in research to obtain advanced scientific knowledge of new drug o No plan to market the product 7
CONTENT OF IND In three broad areas: Animal Pharmacology and Toxicology Studies o An assessment as to whether the product is reasonably safe for initial testing in humans o Any previous experience with the drug in humans Manufacturing Information o composition, manufacturer, stability, and controls used for manufacturing the drug Clinical Protocols and Investigator Information o Commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations. Once the IND is submitted, the sponsor must wait 30 days before initiating any clinical trials. During this time, FDA opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk has an 8
FORMAT OF INDA Cover sheet (Form FDA-1571) Name, address, telephone of sponsor Identification of phases Commitment not to begin CT until IND approval Commitment by IRB- Form 56 Commitment for conducting CT- accordance with regulations Name, title Monitor Name, title person(s) for reviewing Name, Address of CRO, if any Signature of sponsor Table of contents Introductory statement & general investigational plan Investigatorsbrochure Study protocol Investigatorfacilities & IRB data Chemistry manufacturing & control data H.Pharmacology & toxicologydata I. P 19r-e 06v-2i0o1u 6s human experience A. o o o o o o o o o B. C. D. E. F. G.
Resources For INDApplications Pre-InvestigationalNew DrugApplication (IND) Consultation Program o Offered by CDER (Center for Drug Evaluation and Research) to foster early communications between sponsors and new drug review divisions in order to provide guidance on the data necessary to warrant IND submission. Guidance Documents for INDs o documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products 10
GUIDANCE DOCUMENTS ForThe Complete List Of CDER Guidance, Please See The Guidance Index Safety Reporting Requirements for INDs and BE/BAStudies CGMPfor Phase 1 Investigational Drugs Exploratory IND Studies Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well Characterized, Therapeutic, Biotechnology-Derived Products Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including Well- Characterized,Therapeutic, Biotechnology-Derived Products Bioavailability and Bioequivalence Studies for OrallyAdministered Drug Products IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer Guideline for Drug Master Files A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Required Specifications for FDA's IND, NDA, andANDADrug Master File Binders Immunotoxicology Evaluation of Investigational New Drugs 19-06-2016 SagarKishorSavale 11
Laws, regulations, Policies, Procedures The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive. 12
Laws, regulations, Policies, Procedures Code Of Federal Regulations (CFR) o The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR. o The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. o The FDA's portion of the CFR interprets the The Federal Food, Drug, and Cosmetic Act and related statutes. Section 21 of the CFR contains most regulations pertaining to food and drugs. 21CFRPart312 Investigational New Drug Application INDAand NDAApplicationsforFDA Approvalto Market a New Drug(New DrugApproval) 21CFRPart314 21CFRPart316 OrphanDrugs 21CFRPart58 Good LabPractice for NonclinicalLaboratory [Animal]Studies 21CFRPart50 Protectionof HumanSubjects 21CFRPart56 InstitutionalReviewBoards 21CFRPart201 DrugLabeling 21CFRPart54 FinancialDisclosure byClinicalInvestigators 13
Laws, regulations, Policies, Procedures CDER's Manual of Policies and Procedures (MaPPs) MaPPS are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities. 14
INDAReview Process 19-06-2016 SagarKishorSavale 15
DRUG DEVELOPMENT PROCESS 19-06-2016 SagarKishorSavale 16
New Drug Development and Review Process Steps from Test Tube to New DrugApplication Review 17
Phases of clinical testing Numberof patients Length Purpose Percent successfully completing Phase Phase 1 20-100 Several months Mainlysafety 67 Phase 2 Up toseveral hundred Several months to two years Someshort- term safety but mainly effectiveness Safety, effectiveness, dosage 45 Phase 3 Several hundred toseveral thousand 1-4years 5-10 19-06-2016 SagarKishorSavale 18
Clinical Trials 10-15 years from lab to US patients Only 1 in 5000 compounds make it to human testing Only 1 in 5 tested in humans is approved Testing Phases in Humans DISCOVERY Phase I RESEARCH Phase II DEVELOPMENT Phase III CLINICALSTUDIES Phase IV MEDICINEAPPROVED 19
Introductory statement Description of the investigational drug All active ingredients Drug s pharmacological classification Structuralformula Route of administration Summary of previous human experience Formulation of dosage forms Objective and planned duration of proposed clinical investigation. 20
Investigational plan Description of clinical studies planned for the experimental drug Purpose of the study Indication to be studied Types of trials to be initiated 1.Number of study subjects 2.Risks involved 21
INVESTIGATORS BROCHURE Structural formula of drug. Summary of pharmacological , toxicological , pharmacokinetic effects in animals. Safety and efficacy Purpose of study Dose / dose frequency Monitoring procedures 22
Clinical protocol Aclinical protocol describes how a particular clinical trial is to be conducted. It describes the objectives of study the trial design how subjects are selected how the trial is to be carried out 23
It should contain the following elements: Astatement of the objective and purpose of study. Name , address and qualification of each investigator participating in the study. Name and address of each clinical site. Study subject inclusion and exclusion criteria. Estimate of the number of subjects to be enrolled in the study. 24
Chemistry, manufacturing and Control Data Determines the adequacy of methods used to manufacture and assay investigational compound Safety concerns Describe drug substances Method of preparation Reagent and solvents Acceptable limits and analytical methods to ensure quality and purity of drug. 25
Pharmacological and Toxicology data : Pharmacology and drug disposition Integrated toxicology summary Previous human exposure : Marketed (foreign) or previously tested in humans. 26
FDAReview of The INDA Once the ind is stamped as received ,it is sent to the review division within CDER. On arrival at the review division , it is critically evaluated by several reviewers of Chemisty Biopharmaceutics Medical Stastistics Microbiology Pharmacology /toxicology sections
All these areas review the data submitted with the primary purpose to ensure safety of the individual enrolled in th e study. Once an IND is submitted,the study can t be initiated until a period of 30 days. If there are any major issues relating to the safety of the volunteers in the proposed study , the FDAcan institute a clinical hold. 28
INDAAnnual reports Sponsors should submit an annual report that provides the FDAwith a brief update on the progress of all investigations included in the IND. It should contain the following: Individual study information. Summary of the study. Listing of any significant foreign marketing developments with the drug e.g. approval in another country. 29
